Osteoporosis is a common condition in adults which is evidenced by a decrease in bone density throughout the body. In fact, both the bone mineral (calcium phosphate called "hydroxyapatite") and the matrix (major protein called "collagen") are slowly lost. This condition may begin to occur in humans as early as age 30. In general, the process is more rapid in women than in men. However, after age 80 there is no sex difference in the incidence of osteoporosis. In the course of 10 to 20 years of bone loss there may be symptoms of back pain and X-ray evidence of deformation of the back bone. At older ages, the brittleness of the bones become evident by the ease in which the pelvis and femur fractures and the slowness of their subsequent healing. Osteoporosis is the most common cause of fractures in people over age 45.
Although the cause of osteoporosis is poorly understood, it is believed that there is an imbalance between bone production and bone resorption (bone break-down). Bone remains a dynamic tissue throughout the life of an animal. That is, new bone is continuously being formed and old bone is continuously being resorbed. However, in animals suffering from an osteoporotic condition, bone resorption exceeds bone formation.
A survey indicates that in the United States there may be four million osteoporotic patients with serious symptoms such as vertebral fractures (D. Whedon, Clinical Endocrinology, II, 349-376 (1968). Moreover, it is estimated that there are currently another 10 million persons suffering from osteoporosis who have not yet developed symptoms. Various types of osteoporosis are designated according to special conditions believed to be causative: senile (aging); post-menopausal (female loss of estrogenesis); disuse (chronic immobilization); steroid (long term steroid treatment as in arthritis). Osteoporosis may also be manifested in dental problems since the mandible appears to lose mass more rapidly than any other bone. Thus, periodontal disease involving a loosening of the adult teeth may be an early sign of osteoporosis.
The mechanism of bone loss is at present poorly understood. Moreover, the present methods of treatment are generally unsatisfactory. These include anabolic agents, various drugs containing phosphorus, Vitamin D, estrogens, calcium salts, fluorides and calcitonin.
Anabolic agents and estrogen replacement therapy have been the therapy of choice for osteoporosis in post-menopausal women. Unfortunately, recent studies have suggested that patients taking only estrogens may have an increased risk of endometriosis. Hence, the advisability of long-term use of such treatment is questioned by some practitioners.
Physical therapy is another method currently used to treat osteoporosis since immobilization can cause osteoporosis at any age. Thus, many physicians believe that exercise and physical therapy can prevent the progression of the disease in elderly patients. However, physical therapy can be harmful for patients with fractures and, moreover, overstrenuous exercise can cause fractures in patients with severe osteoporosis.
Other treatments include the administration of a fluoride salt such as sodium fluoride which has been shown to promote bone growth clinically, apparently by stimulating collagen synthesis. However, a serious side effect is poorly calcified, irregular bone growth. Another treatment involves infusion of calcium and Vitamin D to counteract the deficiency of calcium or impaired absorption of calcium which is symptomatic in some elderly patients. There is, however, no evidence that a higher intake of calcium will prevent osteoporosis or increase bone mass and it could increase urinary calcium excretion.
The most promising therapeutic approach to the treatment of osteoporosis is the administration of agents which have been designed to modify the balance between the rate of bone production and the rate of bone resorption in such a manner that the ratio of the former to the latter is increased, resulting in no net bone loss. After the previously occurred bone losses have been restored, a steady state is reached where the rate of bone production and rate of bone resorption are equal. Such a modification may be effected by stimulating the physiological mechanism of bone deposition, i.e., bone formation, or by retarding the mechanism of bone resorption, or both. Drugs presently in use or in the experimental stages for accomplishing these purposes include inorganic phosphate type drugs, calcitonin and mithramycin. However, all of these drugs suffer serious drawbacks.
Mithramycin, an antibiotic, has anti-tumor activity together with hypocalcemic activity, effecting a lowering of serum calcium which in turn is believed to be indicative of a decrease in the relative rate of bone resorption--i.e., bone resorption relative to bone production. Side effects, however, include renal and hepatic toxicity as well as nausea. Likewise, the inorganic phosphates (called "phosphonates") have side effects which include extraskeletal calcification, hypotension and renal failure. Calcitonin presents an immunological problem because it is derived from a non-human source. Thus, none of the foregoing agents are at present suitable for use alone in the treatment of osteoporosis.